Abstract
In an attempt to elucidate the mechanism of neuroleptic action, effects of chlorpromazine, haloperidol and pimozide on the dopaminergic and cholinergic systems in bullfrog and rabbit sympathetic ganglia were investigated with extracellular and intracellular techniques. In bullfrog ganglia, chlorpromazine (10-5 M) and haloperidol (10-5 M) caused a reversible depression of P and LN waves but no changes in LLN wave. Pimozide (10-5 M) was without effect on P wave and other slow postsynaptic potentials. The resting properties of amphibian ganglion cells were affected by none of these drugs, while action potentials were depressed slightly in a small number of cells by chlorpromazine (10-5 M) and haloperidol (10-5 M). The latter two drugs reversibly inhibited both the fast (nicotinic) and slow (muscarinic) depolarization of the cell membrane induced by iontophoretic application of acetylcholine. It was surmised, therefore, that the depression of P wave in the presence of chlorpromazine or haloperidol was mainly due to an impairment of the muscarinic transmission from preganglionic fibers to SIF cells (chromaffin-like interneurons). In contrast to the amphibian preparation, P and LN waves of rabbit ganglia were unaffected by the neuroleptics (10-5 M). Moreover, the dopamine-induced postsynaptic hyperpolarization as well as the dopamine-elicited presynaptic inhibition were well maintained in the medium containing chlorpromazine, haloperidol or pimozide (10-5 M). These results demonstrate that the pre- and postsynaptic dopamine receptors with an inhibitory capacity are insensitive to the blocking action of neuroleptics. This leaves a possibility that dopamine receptors with a facilitatory function might be a candidate for the site of neuroleptic action.
